1887

Abstract

In fungi, nonribosomal peptide synthetases (NRP synthetases) are large multi-functional enzymes containing adenylation, thiolation (or peptidyl carrier protein, PCP) and condensation domains. These enzymes are often encoded within gene clusters. Multiple NRP synthetase ORFs have also been identified in fungi (14 in ). LeaA, a methyltransferase, is involved in secondary metabolite gene cluster regulation in spp. The NRP synthetases GliP and FtmA respectively direct the biosynthesis of the toxic metabolites gliotoxin and brevianamide F, a precursor of bioactive prenylated alkaloids. The NRP synthetase Pes1 has been shown to mediate resistance to oxidative stress, and in plant-pathogenic ascomycetes (e.g. ) an NRP synthetase, encoded by the gene, significantly contributes to virulence and resistance to oxidative stress. Adenylation (A) domains within NRP synthetases govern the specificity of amino acid incorporation into nonribosomally synthesized peptides. To date there have only been limited demonstrations of A domain specificity (e.g. GliP and in ) in fungi. Indeed, only prediction data are available on A domain specificity of NRP synthetases from most fungi. NRP synthetases are activated by 4′-phosphopantetheinylation of serine residues within PCP domains by 4′-phosphopantetheinyl transferases (4′-PPTases). Coenzyme A acts as the 4′-phosphopantetheine donor, and labelled coenzyme A can be used to affinity-label apo-NRP synthetases. Emerging fungal gene disruption and gene cluster expression strategies, allied to proteomic strategies, are poised to facilitate a greater understanding of the coding potential of NRP synthetases in fungi.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2006/006908-0
2007-05-01
2019-10-22
Loading full text...

Full text loading...

/deliver/fulltext/micro/153/5/1297.html?itemId=/content/journal/micro/10.1099/mic.0.2006/006908-0&mimeType=html&fmt=ahah

References

  1. Balibar, C. J. & Walsh, C. T. ( 2006; ). GliP, a multimodular nonribosomal peptide synthetase in Aspergillus fumigatus, makes the diketopiperazine scaffold of gliotoxin. Biochemistry 45, 15029–15038.[CrossRef]
    [Google Scholar]
  2. Bok, J. W. & Keller, N. P. ( 2004; ). LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot Cell 3, 527–535.[CrossRef]
    [Google Scholar]
  3. Bok, J. W., Balajee, S. A., Marr, K. A., Andes, D., Nielsen, K. F., Frisvad, J. C. & Keller, N. P. ( 2005; ). LaeA, a regulator of morphogenetic fungal virulence factors. Eukaryot Cell 4, 1574–1582.[CrossRef]
    [Google Scholar]
  4. Bok, J. W., Noordermeer, D., Kale, S. P. & Keller, N. P. ( 2006a; ). Secondary metabolic gene cluster silencing in Aspergillus nidulans. Mol Microbiol 61, 1636–1645.[CrossRef]
    [Google Scholar]
  5. Bok, J. W., Hoffmeister, D., Maggio-Hall, L. A., Murillo, R., Glasner, J. D. & Keller, N. P. ( 2006b; ). Genomic mining for Aspergillus natural products. Chem Biol 13, 31–37.[CrossRef]
    [Google Scholar]
  6. Bok, J. W., Chung, D., Balajee, S. A., Marr, K. A., Andes, D., Nielsen, K. F., Frisvad, J. C., Kirby, K. A. & Keller, N. P. ( 2006c; ). GliZ, a transcriptional regulator of gliotoxin biosynthesis, contributes to Aspergillus fumigatus virulence. Infect Immun 74, 6761–6768.[CrossRef]
    [Google Scholar]
  7. Brakhage, A. A. & Langfelder, K. ( 2002; ). Menacing mold: the molecular biology of Aspergillus fumigatus. Annu Rev Microbiol 56, 433–455.[CrossRef]
    [Google Scholar]
  8. Brookman, J. L. & Denning, D. W. ( 2000; ). Molecular genetics in Aspergillus fumigatus. Curr Opin Microbiol 3, 468–474.[CrossRef]
    [Google Scholar]
  9. Capon, R. J., Ratnayake, R., Stewart, M., Lacey, E., Tennant, S. & Gill, J. H. ( 2005; ). Aspergillazines A–E: novel heterocyclic dipeptides from an Australian strain of Aspergillus unilateralis. Org Biomol Chem 3, 123–129.[CrossRef]
    [Google Scholar]
  10. Challis, G. L., Ravel, J. & Townsend, C. A. ( 2000; ). Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains. Chem Biol 3, 211–224.
    [Google Scholar]
  11. Couch, R., O'Connor, S. E., Seidle, H., Walsh, C. T. & Parry, R. ( 2004; ). Characterization of CmaA, an adenylation-thiolation didomain enzyme involved in the biosynthesis of coronatine. J Bacteriol 186, 35–42.[CrossRef]
    [Google Scholar]
  12. Coyle, C. M. & Panaccione, D. G. ( 2005; ). An ergot alkaloid biosynthesis gene and clustered hypothetical genes from Aspergillus fumigatus. Appl Environ Microbiol 71, 3112–3118.[CrossRef]
    [Google Scholar]
  13. Cramer, R. A., Jr, Gamcsik, M. P., Brooking, R. M., Najvar, L. K., Kirkpatrick, W. R., Patterson, T. F., Balibar, C. J., Graybill, J. R., Perfect, J. R. & other authors ( 2006a; ). Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production. Eukaryot Cell 5, 972–980.[CrossRef]
    [Google Scholar]
  14. Cramer, R. A., Jr, Stajich, J. S., Yamanaka, Y., Dietrich, F. E., Steinbach, W. J. & Perfect, J. R. ( 2006b; ). Phylogenomic analysis of non-ribosomal peptide synthetases in the genus Aspergillus. Gene 383, 24–32.[CrossRef]
    [Google Scholar]
  15. Dean, R. A., Talbot, N. J., Ebbole, D. J., Farman, M. L., Mitchell, T. K., Orbach, M. J., Thon, M., Kulkarni, R., Xu, J. R. & other authors ( 2005; ). The genome sequence of the rice blast fungus Magnaporthe grisea. Nature 434, 980–986.[CrossRef]
    [Google Scholar]
  16. Di Vincenzo, L., Grgurina, I. & Pascarella, S. ( 2005; ). In silico analysis of the adenylation domains of the freestanding enzymes belonging to the eucaryotic nonribosomal peptide synthetase-like family. FEBS J 272, 929–941.[CrossRef]
    [Google Scholar]
  17. Dorrestein, P. C., Blackhall, J., Straight, P. D., Fischbach, M. A., Garneau-Tsodikova, S., Edwards, D. J., McLaughlin, S., Lin, M., Gerwick, W. H. & other authors ( 2006; ). Activity screening of carrier domains within nonribosomal peptide synthetases using complex substrate mixtures and large molecule mass spectrometry. Biochemistry 45, 1537–1546.[CrossRef]
    [Google Scholar]
  18. Eisendle, M., Oberegger, H., Zadra, I. & Haas, H. ( 2003; ). The siderophore system is essential for viability of Aspergillus nidulans: functional analysis of two genes encoding l-ornithine N 5-monooxygenase (sidA) and a non-ribosomal peptide synthetase (sidC). Mol Microbiol 49, 359–375.[CrossRef]
    [Google Scholar]
  19. Eley, K. L., Halo, L. M., Song, Z., Powles, H., Cox, R. J., Bailey, A. M., Lazarus, C. M. & Simpson, T. J. ( 2007; ). Biosynthesis of the 2-pyridone tenellin in the insect pathogenic fungus Beauveria bassiana. ChemBioChem 8, 289–297.[CrossRef]
    [Google Scholar]
  20. Fox, M., Gray, G., Kavanagh, K., Lewis, C. & Doyle, S. ( 2004; ). Detection of Aspergillus fumigatus mycotoxins: immunogen synthesis and immunoassay development. J Microbiol Methods 56, 221–230.[CrossRef]
    [Google Scholar]
  21. Galagan, J. E., Calvo, S. E., Cuomo, C., Ma, L. J., Wortman, J. R., Batzoglou, S., Lee, S. I., Basturkmen, M., Spevak, C. C. & other authors ( 2005; ). Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 438, 1105–1156.[CrossRef]
    [Google Scholar]
  22. Gardiner, D. M. & Howlett, B. J. ( 2005; ). Bioinformatic and expression analysis of the putative gliotoxin biosynthetic gene cluster of Aspergillus fumigatus. FEMS Microbiol Lett 248, 241–248.[CrossRef]
    [Google Scholar]
  23. Gardiner, D. M., Cozijnsen, A. J., Wilson, L. M., Pedras, M. S. & Howlett, B. J. ( 2004; ). The sirodesmin biosynthetic gene cluster of the plant pathogenic fungus Leptosphaeria maculans. Mol Microbiol 53, 1307–1318.[CrossRef]
    [Google Scholar]
  24. Gardiner, D. M., Waring, P. & Howlett, B. J. ( 2005; ). The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis. Microbiology 151, 1021–1032.[CrossRef]
    [Google Scholar]
  25. Grunewald, J. & Marahiel, M. A. ( 2006; ). Chemoenzymatic and template-directed synthesis of bioactive macrocyclic peptides. Microbiol Mol Biol Rev 70, 121–146.[CrossRef]
    [Google Scholar]
  26. Guo, S. & Bhattacharjee, J. K. ( 2003; ). Molecular characterization of the Candida albicans LYS5 gene and site-directed mutational analysis of the PPTase (Lys5p) domains for lysine biosynthesis. FEMS Microbiol Lett 224, 261–267.[CrossRef]
    [Google Scholar]
  27. Guo, S., Evans, S. A., Wilkes, M. B. & Bhattacharjee, J. K. ( 2001; ). Novel posttranslational activation of the LYS2-encoded alpha-aminoadipate reductase for biosynthesis of lysine and site-directed mutational analysis of conserved amino acid residues in the activation domain of Candida albicans. J Bacteriol 183, 7120–7125.[CrossRef]
    [Google Scholar]
  28. Haarmann, T., Machado, C., Lubbe, Y., Correia, T., Schardl, C. L., Panaccione, D. G. & Tudzynski, P. ( 2005; ). The ergot alkaloid gene cluster in Claviceps purpurea: extension of the cluster sequence and intra species evolution. Phytochemistry 66, 1312–1320.[CrossRef]
    [Google Scholar]
  29. Han, K. H., Kim, J. H., Kim, W. S. & Han, D. M. ( 2005; ). The snpA, a temperature-sensitive suppressor of npgA1, encodes the eukaryotic translation release factor, eRF1, in Aspergillus nidulans. FEMS Microbiol Lett 251, 155–160.[CrossRef]
    [Google Scholar]
  30. Harrison, P., Kumar, A., Lan, N., Echols, N., Synder, M. & Gerstein, M. ( 2002; ). A small reservoir of disabled ORFs in the yeast genome and its implications for the dynamics of proteome evolution. J Mol Biol 316, 409–419.[CrossRef]
    [Google Scholar]
  31. Hicks, L. M., Mazur, M. T., Miller, L. M., Dorrestein, P. C., Schnarr, N. A., Khosla, C. & Kelleher, N. L. ( 2006; ). Investigating nonribosomal peptide and polyketide biosynthesis by direct detection of intermediates on >70 kDa polypeptides by using Fourier-transform mass spectrometry. ChemBioChem 7, 904–907.[CrossRef]
    [Google Scholar]
  32. Hissen, A. H., Wan, A. N., Warwas, M. L., Pinto, L. J. & Moore, M. M. ( 2005; ). The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding l-ornithine N 5-oxygenase, is required for virulence. Infect Immun 73, 5493–5503.[CrossRef]
    [Google Scholar]
  33. Jegorov, A., Hajduch, M., Sulc, M. & Havlicek, V. ( 2006; ). Nonribosomal cyclic peptides: specific markers of fungal infections. J Mass Spectrom 41, 563–576.[CrossRef]
    [Google Scholar]
  34. Kelleher, N. L. & Hicks, L. M. ( 2005; ). Contemporary mass spectrometry for the direct detection of enzyme intermediates. Curr Opin Chem Biol 9, 424–430.[CrossRef]
    [Google Scholar]
  35. Keller, N. P. G., Turner, G. & Bennet, J. W. ( 2005; ). Fungal secondary metabolism – from biochemistry to genomics. Nat Rev Microbiol 3, 937–947.[CrossRef]
    [Google Scholar]
  36. Keszenman-Pereyra, D., Lawrence, S., Twfieg, M. E., Price, J. & Turner, G. ( 2003; ). The npgA cfwA gene encodes a putative 4-phosphopantetheinyl transferase which is essential for penicillin biosynthesis in Aspergillus nidulans. Curr Genet 43, 186–190.
    [Google Scholar]
  37. Khoufache, K., Puel, O., Loiseau, N., Delaforge, M., Rivollet, D., Coste, A., Cordonnier, C., Escudier, E., Botterel, F. & Bretagne, S. ( 2007; ). Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells. BMC Microbiol 7, 5 [CrossRef]
    [Google Scholar]
  38. Kontoyiannis, D. P. & Bodey, G. P. ( 2002; ). Invasive aspergillosis in 2002: an update. Eur J Clin Microbiol Infect Dis 21, 161–172.[CrossRef]
    [Google Scholar]
  39. Kosalec, I., Klaric, M. S. & Pepeljnjak, S. ( 2005; ). Verruculogen production in airborne and clinical isolates of Aspergillus fumigatus. Acta Pharm 55, 357–364.
    [Google Scholar]
  40. Krappmann, S. ( 2006; ). Tools to study molecular mechanisms of Aspergillus pathogenicity. Trends Microbiol 14, 356–364.[CrossRef]
    [Google Scholar]
  41. Kupfahl, C., Heinekamp, T., Geginat, G., Ruppert, T., Hartl, A., Hof, H. & Brakhage, A. A. ( 2006; ). Deletion of the gliP gene of Aspergillus fumigatus results in loss of gliotoxin production but has no effect on virulence of the fungus in a low-dose mouse infection model. Mol Microbiol 62, 292–302.[CrossRef]
    [Google Scholar]
  42. La Clair, J. J., Foley, T. L., Schegg, T. R., Regan, C. M. & Burkart, M. D. ( 2004; ). Manipulation of carrier proteins in antibiotic biosynthesis. Chem Biol 11, 195–201.[CrossRef]
    [Google Scholar]
  43. Lambalot, R. H., Gehring, A. M., Flugel, R. S., Zuber, P., LaCelle, M., Marahiel, M. A., Reid, R., Khosla, C. & Walsh, C. T. ( 1996; ). A new enzyme superfamily – the phosphopantetheinyl transferases. Chem Biol 3, 923–936.[CrossRef]
    [Google Scholar]
  44. Lee, B. N., Kroken, S., Chou, D. Y., Robbertse, B., Yoder, O. C. & Turgeon, B. G. ( 2005; ). Functional analysis of all nonribosomal peptide synthetases in Cochliobolus heterostrophus reveals a factor, NPS6, involved in virulence and resistance to oxidative stress. Eukaryot Cell 4, 545–555.[CrossRef]
    [Google Scholar]
  45. Lewis, R. E., Wiederhold, N. P., Chi, J., Han, X. Y., Komanduri, K. V., Kontoyiannis, D. P. & Prince, R. A. ( 2005; ). Detection of gliotoxin in experimental and human aspergillosis. Infect Immun 73, 635–637.[CrossRef]
    [Google Scholar]
  46. Mabey, J. E., Anderson, M. J., Giles, P. F., Miller, C. J., Attwood, T. K., Paton, N. W., Bornberg-Bauer, E., Robson, G. D., Oliver, S. G. & Denning, D. W. ( 2004; ). CADRE: the Central Aspergillus Data REpository. Nucleic Acids Res 32, 401–405.[CrossRef]
    [Google Scholar]
  47. Machida, M., Asai, K., Sano, M., Tanaka, T., Kumagai, T., Terai, G., Kusumoto, K., Arima, T., Akita, O. & other authors ( 2005; ). Genome sequencing and analysis of Aspergillus oryzae. Nature 438, 1157–1161.[CrossRef]
    [Google Scholar]
  48. Maiya, S., Grundmann, A., Li, S. M. & Turner, G. ( 2006; ). The fumitremorgin gene cluster of Aspergillus fumigatus: identification of a gene encoding brevianamide F synthetase. ChemBioChem 7, 1062–1069.[CrossRef]
    [Google Scholar]
  49. May, J. J., Finking, R., Wiegeshoff, F., Weber, T. T., Bandur, N., Koert, U. & Marahiel, M. A. ( 2005; ). Inhibition of the d-alanine : d-alanyl carrier protein ligase from Bacillus subtilis increases the bacterium's susceptibility to antibiotics that target the cell wall. FEBS J 272, 2993–3003.[CrossRef]
    [Google Scholar]
  50. Mennink-Kersten, M. A., Klont, R. R., Warris, A., Op den Camp, H. J. & Verweij, P. E. ( 2004; ). Bifidobacterium lipoteichoic acid and false elisa reactivity in Aspergillus antigen detection. Lancet 363, 325–327.[CrossRef]
    [Google Scholar]
  51. Mootz, H. D., Schwarzer, D. & Marahiel, M. A. ( 2002; ). Ways of assembling complex natural products on modular nonribosomal peptide synthetases. ChemBioChem 3, 490–504.[CrossRef]
    [Google Scholar]
  52. Mouyna, I., Henry, C., Doering, T. L. & Latgé, J. P. ( 2004; ). Gene silencing with RNA interference in the human pathogenic fungus Aspergillus fumigatus. FEMS Microbiol Lett 237, 317–324.
    [Google Scholar]
  53. Neville, C. M., Murphy, A., Kavanagh, K. & Doyle, S. ( 2005; ). A 4-phosphopantetheinyl transferase mediates non-ribosomal peptide synthetase activation in Aspergillus fumigatus. ChemBioChem 6, 679–685.[CrossRef]
    [Google Scholar]
  54. Nierman, W. C., Pain, A., Anderson, M. J., Wortman, J. R., Kim, H. S., Arroyo, J., Berriman, M., Abe, K., Archer, D. B. & other authors ( 2005; ). Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438, 1151–1156.[CrossRef]
    [Google Scholar]
  55. Oide, S., Moeder, W., Krasnoff, S., Gibson, D., Haas, H., Yoshioka, K. & Turgeon, B. G. ( 2006; ). NPS6, encoding a nonribosomal peptide synthetase involved in siderophore-mediated iron metabolism, is a conserved virulence determinant of plant pathogenic ascomycetes. Plant Cell 18, 2836–2853.[CrossRef]
    [Google Scholar]
  56. Panaccione, D. G. & Coyle, C. M. ( 2005; ). Abundant respirable ergot alkaloids from the common airborne fungus Aspergillus fumigatus. Appl Environ Microbiol 71, 3106–3111.[CrossRef]
    [Google Scholar]
  57. Rausch, C., Weber, T., Kohlbacher, O., Wohlleben, W. & Huson, D. H. ( 2005; ). Specificity prediction of adenylation domains in nonribosomal peptide synthetases (NRPS) using transductive support vector machines (TSVMs). Nucleic Acids Res 33, 5799–5808.[CrossRef]
    [Google Scholar]
  58. Rees, D. O., Bushby, N., Cox, R. J., Harding, J. R., Simpson, T. J. & Willis, C. L. ( 2007; ). Synthesis of [1,2-13C2,15N]-l-homoserine and its incorporation by the PKS-NRPS system of Fusarium moniliforme into the mycotoxin fusarin C. ChemBioChem 8, 6–50.
    [Google Scholar]
  59. Reeves, E. P., Reiber, K., Neville, C., Scheibner, O., Kavanagh, K. & Doyle, S. ( 2006; ). A nonribosomal peptide synthetase (Pes1) confers protection against oxidative stress in Aspergillus fumigatus. FEBS J 273, 3038–3053.[CrossRef]
    [Google Scholar]
  60. Reiber, K., Reeves, E. P., Neville, C., Winkler, R., Gebhardt, P., Kavanagh, K. & Doyle, S. ( 2005; ). The expression of three non-ribosomal peptide synthetases in Aspergillus fumigatus is mediated by the availability of free iron. FEMS Microbiol Lett 248, 83–91.[CrossRef]
    [Google Scholar]
  61. Sanchez, C., Du, L., Edwards, D. J., Toney, M. D. & Shen, B. ( 2001; ). Cloning and characterization of a phosphopantetheinyl transferase from Streptomyces verticillus ATCC15003, the producer of the hybrid peptide-polyketide antitumor drug bleomycin. Chem Biol 8, 725–738.[CrossRef]
    [Google Scholar]
  62. Schardl, C. L. ( 2006; ). A global view of metabolites. Chem Biol 13, 5–6.[CrossRef]
    [Google Scholar]
  63. Schrettl, M. E., Bignell, E., Kragl, C., Joechl, C., Rogers, T., Arst, H. N., Jr, Haynes, K. & Haas, H. ( 2004; ). Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence. J Exp Med 200, 1213–1219.[CrossRef]
    [Google Scholar]
  64. Schwecke, T., Gottling, K., Durek, P., Duenas, I., Kaufer, N. F., Zock-Emmenthal, S., Staub, E., Neuhof, T., Dieckmann, R. & von Dohren, H. ( 2006; ). Nonribosomal peptide synthesis in Schizosaccharomyces pombe and the architectures of ferrichrome-type siderophore synthetases in fungi. ChemBioChem 7, 612–622.[CrossRef]
    [Google Scholar]
  65. Sheppard, D. C., Doedt, T., Chiang, L. Y., Kim, H. S., Chen, D., Nierman, W. C. & Filler, S. G. ( 2005; ). The Aspergillus fumigatus StuA protein governs the up-regulation of a discrete transcriptional program during the acquisition of developmental competence. Mol Biol Cell 16, 5866–5879.[CrossRef]
    [Google Scholar]
  66. Stachelhaus, T., Mootz, H. D. & Marahiel, M. A. ( 1999; ). The specificity-conferring code of adenylation domains in nonribosomal peptide synthetases. Chem Biol 6, 493–505.[CrossRef]
    [Google Scholar]
  67. Tekaia, F. & Latgé, J. P. ( 2005; ). Aspergillus fumigatus: saprophyte or pathogen. Curr Opin Microbiol 8, 385–392.[CrossRef]
    [Google Scholar]
  68. Tobiasen, C., Aahman, J., Ravnholt, K. S., Bjerrum, M. J., Grell, M. N. & Giese, H. ( 2007; ). Nonribosomal peptide synthetase (NPS) genes in Fusarium graminearum, F. culmorum and F. pseudograminearium and identification of NPS2 as the producer of ferricrocin. Curr Genet 51, 43–58.
    [Google Scholar]
  69. Tsunawaki, S., Yoshida, L. S., Nishida, S., Kobayashi, T. & Shimoyama, T. ( 2004; ). Fungal metabolite gliotoxin inhibits assembly of the human respiratory burst NADPH oxidase. Infect Immun 72, 3373–3382.[CrossRef]
    [Google Scholar]
  70. Varga, J., Kocsube, S., Toth, B. & Mesterhazy, A. ( 2005; ). Nonribosomal peptide synthetase genes in the genome of Fusarium graminearum, causative agent of wheat head blight. Acta Biol Hung 56, 375–388.[CrossRef]
    [Google Scholar]
  71. Vigushin, D. M., Mirsaidi, N., Brooke, G., Sun, C., Pace, P., Inman, L., Moody, C. J. & Coombes, R. C. ( 2004; ). Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo. Med Oncol 21, 21–30.[CrossRef]
    [Google Scholar]
  72. Vizcaino, J. A., Sanz, L., Cardoza, R. E., Monte, E. & Gutierrez, S. ( 2005; ). Detection of putative peptide synthetase genes in Trichoderma species: application of this method to the cloning of a gene from T. harzianum CECT 2413. FEMS Microbiol Lett 244, 139–148.[CrossRef]
    [Google Scholar]
  73. Walsh, C. T., Gehring, A. M., Weinreb, P. H., Quadri, L. E. & Flugel, R. S. ( 1997; ). Post-translational modification of polyketide and nonribosomal peptide synthases. Curr Opin Chem Biol 1, 309–315.[CrossRef]
    [Google Scholar]
  74. Weissman, K. J., Hong, H., Oliynyk, M., Siskos, A. P. & Leadlay, P. F. ( 2004; ). Identification of a phosphopantetheinyl transferase for erythromycin biosynthesis in Saccharopolyspora erythraea. ChemBioChem 5, 116–125.[CrossRef]
    [Google Scholar]
  75. Wiest, A., Grzegorski, D., Xu, B. W., Goulard, C., Rebuffat, S., Ebbole, D. J., Bodo, B. & Kenerley, C. ( 2002; ). Identification of peptaibols from Trichoderma virens and cloning of a peptaibol synthetase. J Biol Chem 277, 20862–20868.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2006/006908-0
Loading
/content/journal/micro/10.1099/mic.0.2006/006908-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error